Doctor dinner party talk: vaginal birth or cesarean section?

Last year, on a Wednesday evening in December, one midwife, nineteen doctors, and my software engineer husband assembled in our living room. Well, to be truthful, there were twenty people in the living room and one on Skype.

I had invited them into my home to help me make an important medical decision.

We ate homemade soup and salad, drank a little wine, and took a quick anonymous straw poll: cesarean section or vaginal birth?
 

I was 30 weeks pregnant with a very desired second child-- a pregnancy that I had spent the prior three years working painstakingly to achieve. I had been through one miscarriage, taken fertility medications, undergone several rounds of intrauterine insemination, had laparoscopic uterine surgery to remove a large fibroid, and ultimately went through IVF (thank goodness, it worked!).

Now I was preparing to birth this miracle baby, and I wanted some medical advice. Should I consent to a cesarean section, as was being advised, or should I attempt a vaginal birth?

To be clear, none of my doctors were actually offering me an option. When I signed the consent for my uterine surgery one year prior, I had agreed to the advice that any future pregnancies should be delivered via cesarean section. The fertility doctor told me this, the surgeon told me this, and the governing bodies of medicine (in this case, the American College of Obstetricians and Gynecologists) told me this.

At the time of the fibroid surgery, I was so desperate to be pregnant again that this concession did not matter. But now facing the possibility of yet another abdominal surgery was disconcerting, to say the least. After all, my delivery experience with my first son was uncomplicated and fast-- I was in labor just over six hours, was lucky enough to birth him minutes after reaching the hospital, and was home less than 24 hours later. I recovered well, and I trusted that this birth could be similar.

But what if it wasn't? I did have a big scar on my uterus that hadn't been there last time, and my doctors were unanimous in advising surgery as the only option.

The laparoscopic surgeon quoted a 10% risk of uterine rupture-- that is of 100 women with my type of uterine scar, 10 would rupture-- and this could be serious, very serious. This rate of rupture is about 10 times the rate quoted to women considering a trial of labor after a prior cesarean section.

At my first OB visit, my new doctor quoted the same statistics and reiterated the same recommendation,again pointing to the official word of ACOG, which very clearly advises against vaginal birth in this circumstance.

A uterine rupture could mean emergent surgery, massive blood-loss, hysterectomy, a damaged baby, or even death-- for the baby, for me, or for both of us. Why would I risk such things? Was I totally out of my mind? A cesarean section is not that bad; women have them all the time, most recover well, and (duh) this was a super desired baby. Why couldn't I just accept the recommendation and schedule a c-section?

The answer is not a simple one, as personal risk assessment never is.

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When something medical is happening to me or to someone I love, I find myself repeating a little mantra. It's simple, distracting, and almost always true. It goes something like this:  

This will make me a better doctor. 

This is my mantra for the big things: When my mom was diagnosed with breast cancer. When she had a hip replacement. When my 18-month-old was struggling to breathe in the middle of the night. When I faced three years of secondary infertility. When my father-in-law lost his leg to a flesh-eating bacteria. When my husband found a lump in his breast.

This will make me a better doctor.

It even works for the small things: When my hair fell out postpartum. When my infant got a rash the first time I gave him peanut butter. When my son's belly button looked really wrong after he pushed his poop out too hard. When I have intractable insomnia at 3:30am. When I do three jumping jacks and wet my pants. 

This will make me a better doctor.

It's amazingly reassuring. Powerful in fact. When I frame real life in the context of clinical experience, I feel better about myself, more in control, more doctorly.

Plus, I like to think it's true-- after all, my patients ask on a regular basis two pretty reasonable questions, “Have you had to deal with this before? And “What would you do in this situation?”

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The days leading up to my dinner party were pretty exciting for my internal geek. I had sent out a study guide, a stack of journal articles, my actual operative report, an email from my doctor with her recommendation, and a summary table that I had created. My similarly geeky colleagues rose to the occasion. Several medical friends from out of town sent me long emails with annotated opinions and additional references. That morning, I received two calls with clarifying questions:  Exactly how long ago was your surgery? What risk did the surgeon quote you? And a few texts during my workday: What is your BMI? How far along were you when you went into labor with your first?

I am so blessed-- if only every one of my patients making medical decisions had a cadre of 20 trusted colleague to consult-- and not mere colleagues, but brilliant forward-thinking people who also love me and want what is best for me.

I am also cursed-- cursed by knowing too much, knowing that medicine is fallible and that medical recommendations often come from consensus or precedent rather than evidence or patients' best interests. I know that we are seriously risk averse in medicine (particularly in birth) and that fear of what could possibly happen looms over what is more likely to happen.

I know that evidence-based medicine is only as good as the evidence we have; so often, the data is either lacking or extrapolated. And that informed consent-- while held up as one of the most important principles of Western medicine-- is undervalued in every day practice. When was the last time a physician really went through the evidence with you on the flu vaccine or your mammogram? When did someone really explain the risks versus benefits of taking a cholesterol-lowering medication? When did the surgeon tell you how likely your sore knee would feel better after a clean-out?

This stuff (i.e. risk) is really hard to talk about!

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I love data. I love studies. I love information.

I'm an evidence-based medicine girl at heart. My patients and colleagues are accustomed to hearing me reference the medical literature ad nauseam. Shadow me for an hour or two, and you could record the number of times I say things akin to "Studies show" or "The data is clear" or "The evidence is not really there."

But, to be perfectly honest, when we were talking about my uterus and my post-operative recovery and my risk of death and my risk of long-term complications, the numbers began to feel arbitrary. The bulk of my decision became focused more on matters of faith than of science.

The truth is that I believed in my uterus. I believed in my birthing potential. I believed my baby and I would be okay. But I couldn't sort out whether I was basing my decision on too much magical thinking or too little critical thinking.

In my case, US experts have decided that a 10% risk of uterine rupture is too risky to offer women a choice but that 1% is acceptable. A trial of labor after cesarean section is considered relatively safe when attempted in the prepared environment, but a trial of labor after myomectomy is considered too risky. What does 10% risk of rupture even mean?  Ninety percent actually seems reasonably good odds, particularly considering my history.

Discretionary cutoffs do not feel very scientific to me, but such cutoffs are the foundation of many recommendations in medicine-- at some point, someone has to decide. What is a "normal" vitamin D level? What is an "acceptable" false positive rate with mammography? What percentage of falsely positive genetic screening tests are we "willing to tolerate" to not miss an abnormal baby?

To make matters worse, my reading of the literature on the topic of vaginal birth after uterine surgery was quite different from that of my expert/surgeon and my expert/obstetrician. Of course, I was deeply personally invested and not at all objective. But the more I read, the more disappointed I was in others' understanding of the information. When I read the primary articles (and I consumed all of them), I found that though officials consistently quote a 10% uterine rupture rate, this clinical question had never actually been studied in the United States. The quoted risk was entirely theoretical.
I discovered that in Europe and in Asia, the very question I was asking had been studied in several smallish papers and that their conclusions were different than my doctors' conclusions. In Japan, doctors gave 221 women who had had the same surgery I had the choice of cesarean section vs. attempted vaginal birth. In the end, they had zero uterine ruptures and a vaginal birth rate higher than our vaginal birth rate. In France, doctors did a similar study, and 80% of women managed to birth vaginally; the only uterine ruptures found in women with scars like mine had occurred prior to the onset of labor. In Italy, though women are generally advised to have a cesarean,  it is acceptable to choose to have a vaginal birth; and there too, they have no recorded uterine ruptures. From my read of the literature my risk of uterine rupture was nowhere near 10%. And  while the studies were small, they were reassuring.

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The pre-dinner straw poll came out 12-7. Twelve in favor of vaginal birth. Seven in favor of cesarean section.

I should stop here and give a caveat: all of the physicians present that night were family medicine physicians (two OB friends participated via email). I had invited each person specifically because they were either doing obstetrics as part of their daily jobs or still had a professional interest in birth. Four had done surgical fellowships and performed cesarean sections regularly. A few attend in high risk birth but most take care of low-risk mothers and babies. Many were mothers or fathers themselves. Several had had their own home births.

In other words, I knew I was dealing with a more "pro-vaginal birth" crowd from the get-go and that I would have to take this bias into account. It is not mere coincidence that their general bias was aligned with my own-- after all, they are all my people. I wasn't surprised that the initial vote was 12-7 in favor of vaginal birth, and I was most curious about the seven who voted for c-section. Was it the surgeons? The fathers? Some set who were more risk-averse?

A friend pointed out what he viewed as the most dangerous bias in the room: everyone present that night loved me. That love would clearly influence opinions-- it turns out-- in one of two directions. Some expressed fear that if something happened to me (e.g. my uterus ruptured, and I died), they could never forgive themselves for voting for a vaginal birth. Others expressed that their love for me and my desires made them want what I wanted, and since I clearly wanted a vaginal birth, they had to go along with that.

The discussion was lively. People were engaged. We divided into small groups and dug down deep into the science. There were statements about risk assessment. Conversations about how prepared a hospital really could be for an emergency. People on the web looking for specific details they couldn't quite remember, others passing the charts around. Backs and forths about what the numbers said or didn't say.

I mostly listened-- clarifying a detail here and there-- and watched. It was beautiful-- like an improvisational dance-- brilliant health care professionals doing what they do best: inquiring, probing, dissecting the science, arguing the sides, struggling with the grayness. Engaged, impassioned, and fired up. Those few hours captured exactly why it is that I became a doctor.

A surprising number of people were nervous to take a stand. They were jazzed to discuss the theoretical but when asked to vote publicly almost everyone refused. "Let's do it anonymously," several people cautioned.

Someone asked,"Is the question would I do a vaginal birth or do I think you should? Because I think the answers would be different." Fascinating. Each of these individuals spend most of their days counseling and advising other individuals on risk vs benefits: vaccines, mammograms, antibiotics, surgeries. When we do this twenty times per day, do we ask ourselves these same questions? Do we read so deeply. Do we engage so avidly?

I found myself reassuring the group that I wasn't bound by the vote-- that no matter the outcome, I still maintained choice in the matter.  I wanted what I imagine my own patients want: clear directions when there is one right decision and reasonable options when (as is often the case) there is more than one way to proceed.

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The final (anonymous) vote that night was 12-7. Again twelve in favor of vaginal birth, seven for c-section.

Interestingly, after we were done, four people came up to me and confided that they had flip-flopped by the end of the discussion-- that is, two who had initially voted for c-section went to vaginal birth, and two who had initially voted for vaginal birth went to c-section.

Of all the amazingness that happened that night, the flip flops were the most helpful for my own process. The flip floppers confirmed for me that there wasn't a right answer, that smart thoughtful people can engage in the same material and come up with completely opposite conclusions, and that risk assessment is always personal.

This doesn't mean that decision-making is entirely irrational or that we should abandon the practice of informing our patients or of having educated discussions. It does mean that we patients and we doctors should gather as much information as we can bear to gather, have the benefit of others to help us interpret the information, and ultimately respect that what each individual decides is unique to that individual.

Every decision we make-- be it
health-related or relationship-related or career-related, or even ice cream flavor-related, contains an unmeasurable mixture of critical and magical thinking.

And that is what makes life (and my job) so interesting.

To screen or not to screen, that is the pregnant lady's choice. . .

Screen.
Screen.
Screen.

That's a lot of what I do as a primary care provider: I screen for diabetes, high cholesterol, chlamydia, hearing loss, cervical cancer, obesity, alcohol misuse, depression, breast cancer, domestic violence, obesity, anemia.

I ask a series of questions, sometimes order a lab test or an imaging study, and then, voila!,  I give a literal pat on the patient's back or send a nice letter. "Your blood pressure looks great!" "I am so glad to hear you are exercising regularly!" "Normal pap, due next in 5 years!" "Nice cholesterol, keep up the flax seed oil!" "Nice body mass index, see ya' again next time!"

I love it when the screening tests come back negative.  That's why I pat so enthusiastically and write always using an exclamation mark. My patients love it too.  I feel good about keeping you healthy! You feel good getting a clean bill of health! Happy patient, happy doctor!

Except when the screening test comes back positive.

Then, what do we do?

First, the worry sets in:
Does that mean I have diabetes? Well, it might.
What is wrong with my cervix? We need to do another test to find that out.
Does my baby have a metabolic disorder? We will have to wait for the confirmation, maybe not.
Are you sure that test result isn't wrong--I feel just fine. . .Well, that's why we screen.


Then it can quickly get confusing:
So is this or is this not a problem? Hmmm. . . not sure, I'll get back to you.
Should I be worried? I don't know quite yet.
How invasive is the follow-up test? Let's talk about that.

Is it necessary? Maybe, maybe not.

Do I have the right to refuse? Always, mostly.


All this confusion, concern, and frustration may be lightened (or even avoided) if both patients and physicians ask and answer a few important questions BEFORE anything is ordered and resulted. Here, are those questions: 

1) Should I have the test in the first place?
2) Exactly what information will these tests provide?
3) What would I do in response to what is learned from these tests?

These three questions can be applied to any range of medical evaluations, including, for example, a cholesterol blood test, a cardiac catheterization (aka angiogram), an MRI, and even pee test for your healthy five-year-old. And, in my opinion, not only can they be applied but really they should be considered before the test is ordered.

***

Human beings like diagnostic tests.

While we don't always appreciate the results, we do value the clear and simple answers that come from these tests. Common examples of diagnostic tests with such clear answers include pregnancy tests, throat cultures, and gonorrhea tests. Yes, you are pregnant (wooo hooo!). Yes, you have strep throat (bummer). No, you do not have gonorrhea (phew, thank goodness, thank giddyup!).

But screening tests are a different beast. Screening tests are designed to capture a subset of the population that may be at increased risk for (you fill in the blank) ________ illness or event. They invoke uncertainty. They give a sense something might be wrong, but hold out the possibility that things may be just fine.

In this era of evidence-based medicine, we have more capacity to order more tests, check more levels, offer more studies, more images, and more screening. In theory, these screening tests pick things up early enough to make a difference-- to make the disease curable or treatable or manageable. Many people think more is better, but is that always true? Screening may save you from something as deadly as cancer, but, unfortunately, it's not always as simple.

As our tool set increases in breadth and depth, physicians and patients find ourselves questioning the validity of many of the things we screen, test and treat routinely: breast cancer, pap smears, prostate cancer, aggressively treating blood pressure, how tightly we should control blood sugars. . .even whether or not we should treat strep throat.
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Prenatal Genetic Screening
As an example, I want to explore the intricacies and challenges of decision-making regarding prenatal genetic screening.

Prenatal genetic screening-- that is, checking during pregnancy to see if the developing fetus/embryo/baby is congenitally normal-- has been an ever-expanding field since it emerged in the 1970s. Today, it is standard of care at the first or second prenatal visit, regardless of a mother's age, underlying risks, or medical history, to offer women a range of genetic screening options.

This is my very least favorite part of an OB intake. It goes something like this: "Hi, nice to meet you. Congratulations on your pregnancy. I believe that pregnancy is a unique opportunity for me to care for you and your family during a time of wellness and growth. Pregnancy is a healthy state, and let's do everything in our power to keep you healthy. By the way, do you want me to order tests that will see if that sweet baby growing inside of you is defective?"

(Uh, awkward).

It's hard to delineate exactly what percentage of women are accessing prenatal genetic screening, but by including ultrasound evaluation in the definition, then close to 100% of pregnant women choose to have some part of prenatal genetic screening. If you consider non-invasive blood tests, I estimate about half of my patients choose this form of testing.

I have come to believe that most women choose to do genetic screening for one of three reasons: 1) The prenatal care provider is recommending it as standard of care (and boy do we have some serious super powers to convince people to do all kinds of things they don't normally do (remember that, colleagues, please)). 2) People like tests they feel confident they can pass. Most women assume they will have a normal/negative screen. Rarely I have a patient who is really worried about their genetic screen (usually an older mom, or someone with congenital abnormalities in their family), but these are generally the exception. 3) The risk seems low. These tests are non-invasive, non-traumatic for the growing pregnancy, so. . .well, why not?

A history of prenatal genetic screening
While there was the suggestion by the 1930s that there must be a genetic component to Down Syndrome, it wasn't until the 1960s that scientists finally proved that the cause is a replicated chromosome number 21. Down Syndrome (aka Trisomy 21) remains one of the most common congenital abnormalities among live births and one of the most causes of mental retardation. The predicted rate is 1 in 643 births in the absence of selective termination of affected pregnancies.

In the early 1970s, came the juxtaposition of the chromosomal basis for Down Syndrome with the realization that fetal chromosomes could be examined in the amniotic fluid extract of the mother. Welcome the first amniocentesis for genetic screening-- a test in which amniotic fluid is literally pulled out of a pregnant woman's belly and tested for the presence of chromosomal abnormalities. A paper on the topic published in the still-esteemed New England Journal of Medicine sealed the deal.

The lore is that the maternal age of 35 (often nicknamed "advanced maternal age", a term I HATE HATE as a now 37-year-old pregnant lady, myself) was chosen  because, at the time amniocentesis was introduced, the risk of pregnancy loss (due to amniocentesis) was less than the risk of discovering a genetic abnormality. By 1983, there were simmering ethical discussions encouraging offering amniocentesis to women of all ages, especially as the procedure became less risky.

In the early 1990s non-invasive testing arrived: specifically, maternal fetal serum alpha fetoprotein (aka MF-AFP or just AFP). This was the first test offered to all women (regardless of risk) to evaluate for open neural tube defects in babies. The most common neural tube defect is spina bifida. Historically this blood test was offered in the second trimester (weeks 15-20), at which time if a woman screened "positive" (that is, had an abnormal screen), she would be offered an amniocentesis to confirm the presence of an abnormality.

The AFP was soon expanded to the "triple test" (3 markers) and eventually became the "quad screen" (4 markers), which looks at four markers in mom's blood. These are AFP, HCG, estriol, and inhibin--today, we often refer to the combination as the serum integrated screen or the sequential integrated screen.

In 2007, ACOG decided that ALL women should have access to routine prenatal genetic screening (at a cost of somewhere between $100-$2000 per patient) before 20 weeks (aka 5 months) and women of any age could "opt in" for invasive testing. Invasive testing usually refers to either chorionic villous sampling (or CVS) done between 10th and 12th weeks of pregnancy or amniocentesis (aka amnio) usually done at 15-20 weeks of pregnancy.

It was also in 2007 that ACOG began endorsing the use of nuchal translucency (NT) ultrasound, a specialized ultrasound designed to detect Down Syndrome: the tech literally measures a collection of fluid at the back of the growing fetus' neck and gives you a risk score. Turns out that babies with Down Syndrome tend to have more fluid than babies without, so bigger measurements correspond with increased risk.

Chorionic Villous Sampling (CVS) is a test in which a needle is introduced either through the vagina or through the belly to retrieve some actual cells of the placenta (cells that contain the same genetic material as the baby's cells) and then do genetic testing on those cells. Amniocentesis (often referred to as just Amnio) involves a sampling of cells from the amniotic fluid similarly looking for abnormalities. The benefit of both these tests is their accuracy-- upwards of 99%. The downside is the risk, which is a biggie, miscarriage. It's rare, but still quoted at 1in 200 to 1 in 400. Low risk? Yes, unless you are that one who loses your baby.

And now, in 2014, many women can actually choose non-invasive genetic screening, though not quite covered yet by some insurances, certainly quickly gaining speed. These tests look for actual fetal DNA in a woman's bloodstream (imagine that, your baby's DNA is floating around in your bloodstream) and can do chromosomal analysis really early on and really accurately. As I see it, this is the prenatal genetic testing is definitely the screening test of the future: it can be done as early as 10 weeks gestation and it's really really accurate (>99%) for Trisomy (e.g. Down Syndrome). Only downside is it doesn't test for neural tube defects.

The other test not usually considered prenatal genetic screening but that should also be included is what doctors call "The Fetal Survey" and what most families consider "The ultrasound when you can find out whether you are having a boy or a girl." This is an ultrasound done at 17-20 weeks with a special focus on the baby's anatomy (brain, spinal cord, lips, heart, kidneys, etc). While this isn't traditionally included in the umbrella of prenatal genetic screening, it definitely adds credence to the information gleaned through the other tests. It can also be extremely reassuring to a worried family to "see" normal anatomy in their baby.

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Benefits of prenatal genetic screening

• Increasingly prenatal screening options are non-invasive. Previously women had to weigh risk of losing a baby (miscarriage rate in amniocentesis is quoted as ranging from between 1 in 300 and 1 in 500). Not extremely high but unacceptable if it's you it happens to). Now it's just another blood test, and those of you preggos know you get plenty of those during pregnancy.
• Reassurance that your unborn child is normal. As a parent, believing that your child is healthy is priceless. If things come back confirming that, parents feel really really relieved.
• With earlier and better screening, women have earlier and earlier option to terminate an abnormal pregnancy. Terminating a desired pregnancy is never simple-- but the earlier that decision can be made with the most information possible, the easier on the family. 
• Better preparation for child with birth defects (both emotional and medical management). It is hard for me to imagine a more painful situation than an unanticipated sick new baby. I have been in the room when this unwelcome surprise occurs, and it is terribly painful.
• Increasingly, women are delaying childbirth, thereby increasing the risk of children having genetic abnormalities. These women may be particularly inclined to having the most information possible before a pregnancy progresses.

Risks of prenatal genetic screening

• False positives (unneeded anxiety): if you are talking about the standard screening, there are actually MORE false positive prenatal genetic screens than true positives. That means that more people will be told their screen is abnormal and wind up having a healthy baby, than women who are told their screen is abnormal and have a genetically abnormal child.
• False negative (false reassurance): experienced providers have all experienced a family that had genetic screening and still had an abnormal baby, even one of the diseases picked up by the screening. No test is 100%.
• Screening doesn't pick up all conditions (even genetic abnormalities) but particularly those others that are not chromosomal, for example autism, cerebral palsy, and many other relatively common conditions.
• Doesn't predict severity of disease. Some children with Down Syndrome or Spina Bifida are extremely high functioning. Others require lifelong care. These tests don't shed light on the subtleties of your particular child's health issue. This often is difficult to know even after a child is born.
• Recommended follow-up is invasive testing (including amnio/CVS): people often say "Great, why NOT do a non-invasive test? What's the risk?" The big risk is that if it comes back Screen Positive (aka abnormal), the recommendation is still an invasive test, which has risks including miscarriage. These risks are rare, but it doesn't matter if it happens to you. This is actually changing quite quickly, as the non-invasive tests are gaining ground-- so hopefully this risk is decreasing as I write.
• Stress and anxiety: don't underestimate the power of stress. For every pregnant woman I have ever dealt with who had an abnormal screening test, the world falls down around them. They lose sleep, suffer tremendously, until more information is known. Worry and fear are powerful emotions
• Cost: thankfully, here in California, we have an accessible screening program that is covered by

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And now, enough about prenatal screening. Back to our original questions that I challenge you to ask yourself for each and every test that is being ordered on your behalf:

1) Should I have the test (i.e. prenatal genetic screening) in the first place?
Ooooh, this is a hard one. I get asked this ALL the time when I counsel my patients through this decision-making process for prenatal genetic screening. There is NO right answer. I generally frame it in this way: For some people, having more information is extremely helpful, it enables them to use that information to activate. For others, having more information is anxiety-producing. Which are you? If the test comes back normal, you will be mostly reassured (though, screening tests are not perfect, and all providers can tell you about the time they delivered a baby that had a normal screen and turned out to be congenitally abnormal. Personally, I can also tell you about the time I delivered a baby that we knew was going to be abnormal and is now an almost 3-year-old normal girl.  This part of the decision is super personal.

2) What exactly does this test tell me?
As I discussed above, screening tests are not the same as diagnostic tests. None of the prenatal genetic screening tests (blood tests, ultrasounds) are going to tell you "what your child has". They will only give you a statistical percentage, that may be reassuring, e.g. as a 40 year old woman, you have a 1/500 chance of having a baby with Down syndrome, but based on this test, your individual risk is actually 1/50,000. This risk stratification can definitely be very reassuring-- but there is no guarantee that you will not be that 1 with an abnormal pregnancy.

3) What would I do in response to the results from this test?
This is a very big an important question when it comes to prenatal genetic screening. Though some might suggest that genetic screening is linked with early pregnancy termination (i.e. abortion), the truth is, there are other choices that families might make based on a genetic screen.

For example,
Some might certainly get a diagnostic amniocentesis, while another family might decide they aren't willing to risk an amniocentesis procedure. 
Someone might choose to birth (or not birth) at home.
Someone might choose to see a different level clinician (e.g. a higher level facility).
Some might prepare themselves emotionally for a special needs child.

Whatever your decision, it's worth it to at least consider how a general results may affect your own decision making. To be fair, it is actually very difficult to predict how individuals might respond to abnormal results until those results are sitting right in front of you.

As usual, mostly I encourage you to have an ongoing relationship with your health care provider, discuss the risks and benefits of any testing you are offered, and please ask questions!D It's your body and your decision, after all.
                        

Additional references:
http://embryo.asu.edu/pages/amniocentesis-prior-1980
https://ohiostatepress.org/Books/Complete%20PDFs/Rothenberg%20Women/14.pdf
www.uptodate.com